Coronavirus tests instead of brain research

The Max Planck Institute of Experimental Medicine joins the Covid-19 diagnostic network of Göttingen

April 24, 2020

Model calculations and the example of South Korea in the Covid-19 pandemic show: The spread of the infection can be prevented with widespread population testing for the virus and anti-viral antibodies. The problem is that the capacity for mass testing in Germany is currently insufficient. Scientists at the Max Planck Institute of Experimental Medicine in Göttingen are now using their expertise in the genetic analysis of mice to screen human samples for the coronavirus. They have converted part of their laboratories for the analysis of mucosal swabs and established multiple detection methods.

Samples of human nose swabs. With the LAMP method, SARS-CoV-2-positive samples can be detected by a simple colour change.

Because the Göttingen researchers normally study genetically modified mice, they first had to adapt their methods to the analysis of human tissue. They also reorganized their laboratories to separate the different steps of virus diagnostics.

The Max Planck scientists first checked the reliability of their tests with samples from the Göttingen University Medical Centre. Their results show that they can reliably detect the Sars-CoV-2 virus in patient samples, but not in samples of unaffected probands. “Because the tests are extremely sensitive, usually detecting even a few molecules only, clean controls are extremely important. Otherwise, there is a risk that virus-free samples are falsely classified as infected”, explains Fritz Benseler, whose laboratory at the Max Planck Institute of Experimental Medicine is normally responsible for mouse genotyping, sequence analysis, and nucleic acid synthesis.

Benseler and his team can detect the virus using multiplex and real-time PCR as well as loop-mediated isothermal amplification (LAMP) in samples that they receive from the University Medical Centre Göttingen. “We have many years of experience with multiplex analysis because we use it to genotype large numbers of our genetically modified mice. This method allows us to detect all mutations occurring in a mouse in a single go”, said Benseler. In the same way, the scientists can analyse multiple sections of the viral genome in parallel, add further gene sections as required, or test samples for specific virus variants.

Advantages and disadvantages

Each of the test methods used by the Max Planck researchers has its advantages and disadvantages. In most test laboratories, real-time PCR is used for coronavirus diagnostics. “Especially when setting up our own tests, this method was important for us as a reference”, explains Benseler. However, real-time PCR is relatively complex, and some of the reagents needed for this are in short supply.

Compared with real-time PCR, the LAMP method is relatively simple. In principle, it could even be performed directly on the sample material without prior purification of the viral genome, and because it does not require complex instruments and analytical procedures, it could even be used for field testing. However, it is not yet clear how sensitively and robustly the LAMP method detects Sars-CoV-2. "We are currently comparing the sensitivity of the LAMP method with that of other methods. If these are positive and the supply bottleneck for the LAMP reagents can be overcome, the method could greatly simplify nationwide coronavirus testing”, said Benseler.

Independence from supply bottlenecks

Multiplex PCR analysis of coronavirus samples. The method is not always routine, but it is highly sensitive and can be done without some of the reagents that are becoming increasingly scarce amidst the Covid-19 crisis. The upper diagram shows a positive sample in which four Sars-CoV-2 gene fragments were detected (pink background). In the negative control sample below, only the control gene (human actin) was found.

Multiplex analysis is the “workhorse” of the Max Planck researchers in Göttingen. “For the multiplex analysis we have developed, we can produce the most important reagents for the detection of the viral genome (e.g. primers) in our own laboratory. We are thus relatively independent of supply bottlenecks”, says Nils Brose, Director of the Max Planck Institute for Experimental Medicine. In addition, the necessary enzymes are partly readily available. “We are also getting help from our colleagues at the Max Planck Institute for Biophysical Chemistry in Göttingen, who are now producing large quantities of enzymes and reagents themselves”.

In the meantime, Benseler and his team have analysed the first patient samples. The logistics of sample distribution in Göttingen and the analyses are in place so that Benseler’s group can now help to increase the number of tests and get the spread of Sars-CoV-2 under control. “Because we are not a professional diagnostics laboratory, we are still lacking a few time-saving devices for logistics such as a bar code reader for the sample labels”, says Benseler. Such equipment will now be purchased. The capacity of his laboratory would then increase considerably from the current few hundred samples per day.

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